Hazards posed to the developing fetus and child by exposure to chemical substances are receiving increasing attention. The developmental endpoints examined primarily have been adverse pregnancy outcomes, as well as some consideration of neurobehavioral development. Little is known about normal menstrual function and how it is initiated during adolescence. In this pilot study we propose to examine a measure of sexual development, namely, age at menarche, and its relationship to prenatal exposure to chemical substances including, tobacco smoke, alcohol and caffeine (TAC). Active smoking is a known reproductive hazard during pregnancy and has also been associated with infertility and alterations in hormone excretion levels. Prenatal alcohol exposure is associated with fetal growth retardation and neurologic impairment in offspring. Numerous studies have shown effects of alcohol on the endocrine system of adults and there is suggestive evidence it may effect sexual maturation. Known actions of caffeine present plausible mechanisms for alteration of hormonal profiles and an association with delayed time to conception has been reported. Thus all three exposures may possibly affect sexual development via actions on the prenatal hormonal milieu or the developing nervous system. The proposed pilot study would make use of a large data base of pregnancies ascertained in the early 1960's. Subjects of this study will be the 1000 daughters followed through childhood and adolescence, at which time age at menarche was ascertained. Extensive data was collected prospectively on prenatal exposures, as well as on potential confounders. A number of important exposures and conditions of childhood were also ascertained prospectively, including parental cigarette smoking, childhood behaviors, and growth. With these data we propose to examine whether in utero exposure to TAC or childhood exposure to parental smoking are related to perturbations in age at menarche. Early age at menarche has been associated with an increased risk of breast cancer, thus alteration in menarcheal age may serve as a sentinel of other adverse effects on children's and women's health. Such data will be valuable in designing further studies of the reproductive process and growth and development in relation to early life exposures.